Engineered bacteriophage t4 nanoparticles as a potential targeted activator of hiv-1 latency in cd4+ human t-cells

Abstract

Described is an engineered viral particle programmed with T cell targeting specificity. The viral particles comprise: at least one viral vector, such as bacteriophage T4; and at least one CD4-binding protein displayed on the surface of the viral vector. Also described is a method of reactivate latent HIV-1 and cure patient with HIV-1 infection, using such an engineered viral particle.

What is claimed is: 
     
         1 . An engineered viral particle comprising:
 at least one viral vector; and   at least one CD4 ligand,   wherein the at least one CD4 ligand is displayed on the surface of the at least one viral vector.   
     
     
         2 . The engineered viral particle of  claim 1 , wherein the at least one viral vector is selected from the group consisting of Lambda phage,  Bacillus  phage Phi29,  Escherichia coli  phages T2, T3, T4 and T7, Enterobacteriaphage P22, phage SPP1, Filamentous phages, Herpes viruses, adenoviruses, adeno-associated viruses (AAV), retroviruses, and lentiviruses. 
     
     
         3 . The engineered viral particle of  claim 2 , wherein Filamentous phages are selected from the group consisting of M13, fd, and Fl. 
     
     
         4 . The engineered viral particle of  claim 1 , wherein the CD4 ligand is an HIV component that interact with CD4. 
     
     
         5 . The engineered viral particle of  claim 1 , wherein the CD4 ligand is CD4-binding DARPin (Designed Ankyrin Repeat Proteins) or HIV envelop protein. 
     
     
         6 . The engineered viral particle of  claim 1 , wherein the CD4 ligand is linked to at least one protein selected from the group consisting of Hoc and Soc through a linker. 
     
     
         7 . The engineered viral particle of  claim 6 , wherein the linker is a sequence consisting of 2-25 amino acids. 
     
     
         8 . The engineered viral particle of  claim 6 , wherein the linker projects the CD4 ligand away at least 170 Å distance from the capsid wall of the viral vector. 
     
     
         9 . The engineered viral particle of  claim 6 , wherein the linker is at least one selected from the group consisting of SEQ ID No. 1 and SEQ ID No. 2. 
     
     
         10 . The engineered viral particle of  claim 1 , further comprise at least one nucleic acid packed in the viral vector. 
     
     
         11 . An engineered viral particle comprising:
 at least one viral vector; and   at least one HIV-1 envelope protein,   wherein the at least one HIV-1 envelope protein is displayed on the surface of the at least one viral vector.   
     
     
         12 . The engineered viral particle of  claim 11 , wherein the HIV-1 envelope protein is selected from the group consisting of gp140, gp120, and a fragment of the envelope protein. 
     
     
         13 . A method of activating a latent HIV-1 proviral genome comprising:
 adding an engineered viral particle of  claim 1  to T cells containing latent HIV-1 proviral genome; and   binding the engineered viral particle of  claim 1  with T cells containing latent HIV-1 proviral genome.   
     
     
         14 . The method of  claim 13 , wherein the engineered viral particle does not induce global activation of T cells. 
     
     
         15 . The method of  claim 13 , wherein the engineered viral particle induces transcription of the HIV-1 proviral genome in T cells.